Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder

Xi Zhu, Benjamin Suarez-Jimenez, Amit Lazarov, Liat Helpman, Santiago Papini, Ari Lowell, Ariel Durosky, Martin A. Lindquist, John C. Markowitz, Franklin Schneier, Tor D. Wager, Yuval Neria

Research output: Contribution to journalArticlepeer-review


Background: Recent research suggests that posttraumatic stress disorder (PTSD) is associated with altered amygdala and hippocampal resting-state functional connectivity (rsFC). However, less research has examined whether Prolonged Exposure (PE), a first line exposure-based treatment for PTSD, has the potential to alter resting state neural networks. Methods: A total of 24 patients with PTSD and 26 matched trauma-exposed healthy controls (TEHCs) underwent resting-state functional magnetic resonance imaging (fMRI) at baseline. PTSD patients were scanned a second time after completing 10-session PE in which patients narrated a detailed trauma account (imaginal exposure) and confronted trauma reminders (in vivo exposure) to extinguish trauma-related fear responses. TEHC were scanned again following a 10-week waiting period. Seed regions of interest (ROIs) included centromedial amygdala (CMA), basolateral amygdala (BLA), and the hippocampus. Results: Post- versus pretreatment comparisons indicated increased rsFC of the BLA and CMA with the orbitofrontal cortex (OFC), and hippocampus-medial prefrontal cortex (mPFC) among patients with PTSD, but not among TEHC participants. Conclusions: Enhanced amygdala and hippocampus rsFC with prefrontal cortical regions following PE could underlie improved capacity for inhibition and re-evaluation of threat, and heightened memory encoding and retrieval ability, respectively. These findings encourage further investigation of this circuitry as a therapeutic target in PTSD.

Original languageEnglish
Pages (from-to)974-984
Number of pages11
JournalDepression and Anxiety
Issue number10
StatePublished - Oct 2018
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by grants R01MH072833 and R01MH105355 from the National Institute of Mental Health (NIMH) (Y.N., Principal Investigator), and the New York State Psychiatric Institute. B.S.-J.’s (MH015144) and A.L.’s (MH020004) work is supported by a T32 grant from the NIMH. L.H.’s work is supported by T32 grant MH096724 from the NIMH. Funding from the Donald D. Harrington Fellows Program supported S.P.’s work.

Funding Information:
F.S., J.C.M., and Y.N. are employees of the New York State Psychiatric Institute. J.C.M. has received research support from the Mack Foundation and book royalties from American Psychiatric Publishing, Basic Books, and Oxford University Press. Y.N. has received royalties from Cambridge University Press and Springer, and research support from the Mack Foundation, Stand for the Troops, and the New York Presbyterian Hospital. F.S. has received royalties from Cambridge University Press, Guilford and Uptodate, research support from Forest labs, and honorarium from Elsevier. The authors report no biomedical financial interests or potential conflicts of interest. The authors thank the individuals who contributed to this study: therapists, evaluators, research assistants, volunteers, the personnel of the New York State Psychiatric Institute Anxiety Disorders clinic, and the patients who participated in this treatment study.

Publisher Copyright:
© 2018 Wiley Periodicals, Inc.


  • PTSD
  • amygdala
  • fMRI
  • hippocampus
  • prolonged exposure treatment
  • resting-state functional connectivity

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology


Dive into the research topics of 'Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder'. Together they form a unique fingerprint.

Cite this